The antigen-presentation process constitutes a fundamental basis of the functional immune system in vertebrates. The late
Ralph Steinman, who discovered antigen-presenting dendritic cells, commented about the immune system that, “it is diverse
beyond compare, tolerant without fail, and capable of behaving appropriately with a myriad of infections and other challenges” (1). Significant progress has been made in understanding the classical immune response to infections and rare failings of tolerance
to self (2). However the underlying mechanisms of how the immune system processes and responds to “other challenges,” such as sensing and storage of caloric excess in adipose tissue and the integration of immune system with metabolism, remains
largely unknown. Multiple studies during the past decade have identified visceral adipose tissue as an important site of residence
of leukocytes, including cells of the innate (macrophages and neutrophils) and adaptive immune system (T and B cells) (3–5). It is clear that adipose tissue is a major endocrine organ that controls energy homeostasis.

In addition, the presence of a significant number of hematopoietic cells in adipose tissue suggests that immune cells may
impart unique immunological properties to the adipose tissue (4). For example, 1 g of enzymatically dispersed adipose tissues can contain up to 5 million stromal vascular fraction (SVF)
cells, and after exclusion of adipocytes, ∼50–65% of SVF cells are leukocytes (6). Considering that in severe obesity in humans, the total fat content can constitute up to 50% of the total body mass, adipose
tissue thus represents an uncharacterized immunological organ. For such an immunological characterization, specific cells
in adipose tissue must be able to capture, process, and present antigens to T cells and mount a functional immunological response.
In this issue, Morris et al. (7) further the hypothesis that adipose tissue is immunologically aware by providing tantalizing …